title: Helicobacter pylori genome evolution during human infection.
abstract: High genetic diversity is a hallmark of the gastric pathogen Helicobacter pylori. We used 454 sequencing technology to perform whole-genome comparisons for five sets of H. pylori strains that had been sequentially cultured from four chronically infected Colombians (isolation intervals=3-16 y) and one human volunteer experimentally infected with H. pylori as part of a vaccine trial. The four sets of genomes from Colombian H. pylori differed by 27-232 isolated SNPs and 16-441 imported clusters of polymorphisms resulting from recombination. Imports (mean length=394 bp) were distributed nonrandomly over the chromosome and frequently occurred in groups, suggesting that H. pylori first takes up long DNA fragments, which subsequently become partially integrated in multiple shorter pieces. Imports were present at significantly increased frequency in members of the hop family of outer membrane gene paralogues, some of which are involved in bacterial adhesion, suggesting diversifying selection. No evidence of recombination and few other differences were identified in the strain pair from an infected volunteer, indicating that the H. pylori genome is stable in the absence of mixed infection. Among these few differences was an OFF/ON switch in the phase-variable adhesin gene hopZ, suggesting strong in vivo selection for this putative adhesin during early colonization.
authors.affiliation: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Lynn
authors.initials: L
authors.lastname: Kennemann
authors.forename: Xavier
authors.initials: X
authors.lastname: Didelot
authors.forename: Toni
authors.initials: T
authors.lastname: Aebischer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kuhn
authors.forename: Bernd
authors.initials: B
authors.lastname: Drescher
authors.forename: Marcus
authors.initials: M
authors.lastname: Droege
authors.forename: Richard
authors.initials: R
authors.lastname: Reinhardt
authors.forename: Pelayo
authors.initials: P
authors.lastname: Correa
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Meyer
authors.forename: Christine
authors.initials: C
authors.lastname: Josenhans
authors.forename: Daniel
authors.initials: D
authors.lastname: Falush
authors.forename: Sebastian
authors.initials: S
authors.lastname: Suerbaum
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019143:Evolution, Molecular; D005260:Female; D016680:Genome, Bacterial / Q000502:physiology*; D055106:Genome-Wide Association Study; D042822:Genomic Instability; D016481:Helicobacter Infections / Q000235:genetics* / Q000378:metabolism; D016480:Helicobacter pylori / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide